Objective: The authors sought to clinically describe the relationship of disruptive behavior disorders with both alcohol dependence and the use of a variety of substances. Method: The Child Semi-Structured Assessment for the Genetics of Alcoholism was used to collect data on 54 adolescents with a diagnosis of alcohol dependence. The frequency and age at onset of the disruptive behavior disorder diagnoses were examined as well as age at first use of alcohol, tobacco, marijuana, and other street drugs. Results: Nearly three-quarters of the alcohol-dependent adolescents had at least one disruptive behavior disorder diagnosis. Attention deficit hyperactivity disorder (ADHD) typically occurred first, followed by conduct disorder. Substance use began with alcohol or tobacco, followed by marijuana and then other street drugs. Alcohol dependence began significantly later than the onset of either ADHD or conduct disorder and significantly later than the first use of tobacco. Conclusions: Disruptive behavior diagnoses, particularly conduct disorder, typically precede the initiation of use of a variety of substances that, in turn, precede the diagnosis of alcohol dependence in adolescents.